rs6095516

chr20-49429848-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004975.4(KCNB1):c.567+52066G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,212 control chromosomes in the GnomAD database, including 4,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (4194 hom., cov: 33)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

Genes affected

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB1	NM_004975.4	c.567+52066G>A		intron_variant		ENST00000371741.6
LOC105372649	XR_001754659.2	n.1317+3081C>T		intron_variant, non_coding_transcript_variant
KCNB1	XM_011528799.3	c.567+52066G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+52066G>A		intron_variant		1	NM_004975.4	P1
KCNB1	ENST00000635465.1	c.567+52066G>A		intron_variant		1		P1
	ENST00000637341.1	n.731+3081C>T		intron_variant, non_coding_transcript_variant		5
KCNB1	ENST00000635878.1	c.96+52066G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26963 AN: 152094 Hom.: 4177 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 27011 AN: 152212 Hom.: 4194 Cov.: 33 AF XY: 0.173 AC XY: 12874 AN XY: 74426

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0726

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.142

Alfa AF: 0.174 Hom.: 549

Bravo AF: 0.188

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6095516; hg19: chr20-48046385;